Pharmaceutical compositions comprising three antibiotics

Abstract

Oral administration of a solid dosage form of the present invention comprising an effective amount of rifabutin, an effective amount of clarithromycin, an effective amount of clofazimine, and an effective amount of an absorption enhancer, is used to treat a subject suffering from, or susceptible to, Mycobacterium avium subspecies paratuberculosis infection. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in the increased metabolism of clarithromycin caused by rifabutin. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in the metabolism of rifabutin caused by clarithromycin. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in risk of a subject developing leucopenia or uveitis as a result of rifabutin.

What is claimed is: 
     
       1. A pharmaceutical composition comprising rifabutin, clarithromycin, and a clofazimine-polymer solid dispersion, wherein following oral administration of a total 190 mg of clarithromycin, 90 mg of rifabutin, and 20 mg of clofazimine to a human subject under fed conditions, the composition provides a clarithromycin C max , bioequivalent to about 485 ng/mL, a rifabutin C max  bioequivalent to about 161 ng/mL, and a clofazimine C max  bioequivalent to about 28 ng/mL. 
     
     
       2. The composition of  claim 1  in the form of a capsule. 
     
     
       3. A pharmaceutical composition comprising rifabutin, clarithromycin, and a clofazimine-polymer solid dispersion, wherein following oral administration of a total 190 mg of clarithromycin, 90 mg of rifabutin, and 20 mg of clofazimine to a human subject under fed conditions, the composition provides a clarithromycin AUC 0-inf  bioequivalent to about 3050 ng hr/mL, a rifabutin AUC 0-inf  bioequivalent to about 2048 ng hr/mL, and a clofazimine AUC 0-inf  bioequivalent to about 1031 ng hr/mL. 
     
     
       4. The composition of  claim 1  in the form of a capsule. 
     
     
       5. A pharmaceutical composition comprising rifabutin, clarithromycin, and a clofazimine-polymer solid dispersion, wherein following oral administration of a total 190 mg of clarithromycin, 90 mg of rifabutin, and 20 mg of clofazimine to a human subject under fed conditions, the composition provides a clarithromycin T max  bioequivalent to about 4 hours, a rifabutin T max  bioequivalent to about 6 hours, and a clofazimine T max  bioequivalent to about 8 hours. 
     
     
       6. The composition of  claim 1  in the form of a capsule.